Co-assigned U.S. patent application Ser. No. 06/839,912 (Batt et al.), incorporated herein by reference, discloses 2-substituted-1-naphthols useful as antiinflammatory agents, said compounds having the formula: ##STR1## wherein: R.sup.1 is H, CH.sub.3, Br, Cl, OH, OCH.sub.3, OC.sub.2 H.sub.5, COR.sup.17, COOR.sup.18, CONR.sup.19 R.sup.20, phenyl, --N(R.sup.12)(R.sup.13), ##STR2## S(O).sub.p lower alkyl where p is 0, 1 or 2, or --NHSO.sub.2 lower alkyl optionally substituted with F;
R.sup.2 and R.sup.3 independently are H, CH.sub.3, C.sub.2 H.sub.5, OCH.sub.3, or OC.sub.2 H.sub.5 ; PA0 R.sup.4 is straight-chain or branched alkyl of 1-12 carbons, PA0 R.sup.5 is C.sub.5 -C.sub.7 cycloalkyl, phenyl, COOR.sup.9, OR.sup.9, OC(O)R.sup.9, or C(R.sup.10)(R.sup.11)OR.sup.9, with the proviso that if n=0 then R.sup.5 is not OR.sup.9 or OC(O)R.sup.9 ; PA0 R.sup.6 is C.sub.5 -C.sub.7 cycloalkyl, phenyl, COOR.sup.9, CON(R.sup.12)(R.sup.13), CHO, CN, CH(COOR.sup.9).sub.2, C(R.sup.10)(R.sup.11)OR.sup.9, P(O)(OR.sup.9).sub.2, S(O).sub.w R.sup.9 where w is 0-2 with the proviso that if w=1 then R.sup.9 is not H; SC(NH)NH.sub.2, N(R.sup.12)(R.sup.13), N.sub.3, OR.sup.9, OC(O)R.sup.9, Cl, Br, or I; PA0 R.sup.7 is C.sub.3 -C.sub.8 cycloalkyl ##STR4## where X is S, O, or NR.sup.10, and Y is CH or N; R.sup.8 is C.sub.1 -C.sub.4 alkyl, C.sub.5 -C.sub.7 cycloalkyl, or phenyl; PA0 R.sup.9, R.sup.10, and R.sup.11 are independently H or C.sub.1 -C.sub.4 alkyl; PA0 R.sup.12 and R.sup.13 independently are H, C.sub.1 -C.sub.4 alkyl, or together are (CH.sub.2).sub.4-5 ; PA0 R.sup.14 is H, C.sub.1 -C.sub.4 alkyl, OR.sup.9, O-phenyl, OCH.sub.2 COOR.sup.9, O-benzyl, COOR.sup.9, CF.sub.3, Cl, Br, I, N(R.sup.12)(R.sup.13), or S(O).sub.w R.sup.9 where w is 0-2 with the proviso that if w is 1 then R.sup.9 is not H; PA0 R.sup.15 and R.sup.16 are independently H, C.sub.1-4 alkyl, OR.sup.9, O-benzyl, F, or Cl; PA0 R.sup.17 is lower alkyl, phenyl optionally monosubstituted with Cl, Br, F, CH.sub.3 O, CH.sub.3, pyridyl, thienyl or furyl; PA0 R.sup.18 is H or lower alkyl; PA0 R.sup.19 and R.sup.20 independently are H or lower alkyl, or taken together are (CH.sub.2).sub.4-5 ; and PA0 R.sup.21 is H, lower alkyl, phenyl optionally monosubstituted with Cl, Br, F, CH.sub.3, CH.sub.3 O, pyridyl, thienyl, or furyl; PA0 R.sup.1 is H, alkyl of 1-4 carbon atoms, or benzyl; PA0 R.sup.2 is H or C(.dbd.O)R.sup.4 ; PA0 R.sup.3 is pyridyl, 3,4-methylenedioxyphenyl, a 5-membered, aromatic heterocyclic ring with 1 or 2 heteroatoms selected independently from O, S, N or NR.sup.8, with the proviso that if two heteroatoms are present then one must be N, and if only one is present it cannot be N; or phenyl optionally substituted with 1-3 groups each selected from F, Cl, Br, alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, thioalkyl of 1-4 carbon atoms, alkylsulfonyl of 1-4 carbon atoms, and NR.sup.6 R.sup.7 ; PA0 R.sup.4 is alkyl or alkoxy of 1-4 carbon atoms; PA0 R.sup.6 and R.sup.7 independently are H or alkyl of 1-4 carbon atoms, or taken together are --(CH.sub.2).sub.4 --; and PA0 R.sup.8 is H or alkyl of 1-4 carbon atoms.
straight-chain or branched alkenyl of 2-12 carbons, PA1 straight-chain or branched alkynyl of 2-12 carbons, PA1 cycloalkyl or cycloalkenyl of 5-7 carbons, PA1 CH.sub.2 --C.tbd.C--(CH.sub.2).sub.m R.sup.5 where m is 1-4, PA1 CH.dbd.CH--(CH.sub.2).sub.n R.sup.5 where n is 0-3 and the olefinic bond has either the Z or E configuration PA1 A--R.sup.6, or ##STR3## A is a chain of 2-6 methylene groups optionally substituted at any one of the methylene carbons by a group R.sup.8 ;
or a pharmaceutically suitable salt thereof.
Co-assigned U.S. patent application Ser. No. 07/293,522 (Batt), incorporated herein by reference, discloses substituted indoles useful as antiinflammatory agents, said compounds having the formula: ##STR5## wherein: X is O, S, or NR.sup.1 ;
Further disclosed in these co-assigned applications are topical formulations of the active ingredients useful for treating skin diseases such as psoriasis. However, it has been found that the petrolatum based ointments disclosed therein, result in a high rate of penetration of active ingredient which leads to increased systemic absorption and increased incidence of side effects.
The present invention provides a polyethylene glycol vehicle for the topical administration of the compounds of formula (I) which reduces penetration of active compound but maintains good localized antiinflammatory activity with minimal side effects because of reduced systemic absorption.